The present invention relates to compositions and methods for the repair of periodontal osseous defects. 2. Prior Art
Historically, clinicians have used numerous and varied materials in the attempt to repair periodontal osseous defects. Autogenous grafts have been used with varying degrees of success [Schallhorn, R. G.: Present status of osseous grafting procedures. J. Periodontal 28: 570, 1977; Dragoo, M. R., and Sullivan, H.C.: A clinical and histological evaluation of autogenous iliac bone grafts in humans. Part I, wound healing 2 to 8 months. J Periodontol 44: 599, 1973] but difficulties in obtaining sufficient quantities and the frequent need for a second surgical procedure present obvious disadvantages [Moskow, B. S., Karsh, F., and Stein, S. D.: Histological assessment of autogenous bone--a case report and critical evaluation. J Periodontal 50: 291, 1979.] Allografts [Mellonig, J. T., Bowers, G.M., Bright R. W., and Laurene, J. J.: Clincal evaluation of freeze-dried bone allografts in periodontal osseous defects. J. Periodontal 47: 125, 1976; Sepe, W. W., Bowers, G.M., Lawrence, J. J., Friedlaender, G. E., and Koch, R. W.: Clinical evaluation of freeze-dried bone allografts in periodontal osseous defects. Part II. J Periodontal 49: 9, 1978] have also provided promising results, but limited availability and questions of their immunogenicity still exist [Sanders, J. J., Sepe, W. W., Bowers G. M., Koch, R. W., Williams, J. E., Lekas, J. S., Mellonig, J. T., Pelleu, G. B., Gambill, V.: Clinical evaluation of freeze-dried bone allografts in periodontal osseous defects. Part III. Composite freeze-dried bone allografts with or without autogenous bone grafts. J Periodontal 54: 1, 1983.] In order to overcome these problems, recent attention has been directed toward developing suitable alloplastic materials for such repair procedures.
Tricalcium phosphate ceramic Ca.sub.3 (PO.sub.4).sub.2 (TCP) and Hydroxylapatite ceramic (Ca.sub.10 (PO.sub.4).sub.6 (OH.sub.2) (HA) have been widely investigated. These materials are considered biologically inert, producing no inflammatory response when implanted [Jarcho, M., Bolen, C. H., Thomas, M. B., et al.: Hydroxylapatite synthesis and characterization in dense polycrystalline form. J Mater Sci 11: 2027, 1976; Moskow, B. S., Lubarr, A.: Histological assessment of human periodontal defect after durapatite ceramic implant. J Periodontal 54: 455, 1983; Froum, S. Sj., Kushner, L., Scopp, I.W., and Stahl, S.S.: Human clinical and histologic responses to durapatite implants in intraosseous lesions--case reports. J Periodontal 53:719, 1982; Baldock, W. T., Hutchens, Jr., L. H., McFall, Jr., W. T., Simpson, D. M.: An evaluation of tricalcium phosphate implants in human periodontal osseous defects of two patients, J. Periodontal 56:1, 1985] Rabalais, M. L., Yukna, R.A., and Mayer, E.T. [Evaluation of durapatite ceramic as an alloplatic implant in periodontal osseous defects. I. Initial six month results. J. Periodontal 52: 680, 1981] found, on reentry, greater fill with HA (durapatite) than debridement alone. Others [Nery, E. B., and Lynch, K. L.: Preliminary studies of bioceramic in periodontal osseous defects. J. Periodontal 49: 523, 1978; Strub, J. R., Gaberthuel, T.W. and Firestone, A.R.: Comparison of tricalcium phosphate and frozen allogenic bone implants in man. J Periodontal 50: 624, 1979] have found similar bone fill with TCP. However, histologic evaluations have given little evidence of new attachment with either of these materials [Moskow, B. S., Lubarr, A.: Histological assessment of human periodontal defect after durapatite ceramic implant. J Periodontal 54: 455, 1983; Froum, S. Sj., Kishner, L., Scopp, I. W., and Stahl, S. S.: Human clinical and histologic responses to durapatite implants in intraosseous lesions--case reports. J Periodontal 53: 719, 1982; Meffert, R.M., Thomas, J. R., Hamilton, K. M., Brownstein, C. N.: Hydroxylapatite as an alloplastic graft in the treatment of human periodontal osseous defects. J Peridontal 56: 63-74, 1985.]
Bioactive and biocompatible glasses have been developed as bone replacement materials. Studies have shown that these glasses will induce osteogenesis [Hench, L. L., Splinter, R. J., Allen, W.c. et al: Bonding mechanisms at the interface of ceramic prosthetic materials. J Biomed Mater Res 1971; 5: 117-141; Hench, L. L., Paschall, H.A.: Direct chemical bond of bioactive glass-ceramic materials to bone and muscle. J Biomed Mater Res 1973; 7:25-42; Clark, A.E..COPYRGT.Pantano.COPYRGT.C.G..COPYRGT.and Hench, L. L.: Compositional Analysis of the formation of a bone-implant bond, Symposium on materials for reconstructive surgery, Clemson University, April, 1975; Clark, A. E., Paschall, H. A., and Hence, L. L.: The influence of surface chemistry on implant interface histology; A theorectical basis for implant materials selection, J Biomed Materials Research, Vol. 10, No. 2, pg. 161-174, March, 1976; Hench, L.L., and Wilson, J.: Surface-Active biomaterials. Science 226, pp. 630-636, 1984; Hench, L. L., and Clarke, A.E.: "Adhesion of bone", Biocompatibility of Orthopaedic Implants, Vol. II, Editor-David F. Williams, pg. 129-170, CRC Press, Inc., Boca Raton, Florida, 1982] when implanted in bone. The interfacial bond between the implant and bone has been demonstrated to be extremely strong [Piotrowski, G., Hence, L. L., Allen, W. C., and Miller G. J.: Mechanical Studies of the Bone Bioglass Interfacial Band. J. Biomed Mater Res. Symp, 9: 47-61, 1975.]
The so-called 4555 or S, bioactive glass formulation has been widely tested. The substitution of CaF.sub.2 (calcium fluoride) for a variable percentage of the CaO (calcium oxide) yields the F formulations. Toxicology evaluation of the glasses [summarized by Wilson, J., Schoen, R. J., Pigott, G. H., et al: Toxicology and biocompatibility of bioglasses. J Biomed Mater Res 1981; 805-817] has shown no toxic effects in bone or soft tissue in numerous in vitro and in vivo models.
The bonding of the glass to bone begins with exposure of the glass to aqueous solutions. Na+in the glass exchanges with H+from the body fluids causing the pH to increase. Ca and P migrate from the glass forming a Ca-P rich surface layer. The thickness of the Ca-P rich zone remains at 30-40 microns with an underlying silica rich zone slowly increasing in dimension as the Na+ in the glass continues to exchange with the H+ of the solution.
Initially the Ca-P rich layer is amorphous, but within 7-10 days it crystalizes into an hydroxyapitite-like material. Collagen, either in vitro or in vivo, becomes structurally integrated in the apatite aggomerates. A zone forms between the collagen and surface active glass in vivo that is 80-100 nm thick. Osteoblasts in the implant area provide (1) collagen and ground substance, and (2) matrix vesicles for primary mineralization [Gross, U. M., Strunz, V.: Clin. App. Biomaterials, EDS. Albrektsson and Branemark, J. Wiley, pp. 237, 1982.]As maturation continues, evenly distributed osteocytes can be observed.
The behavior of the bioactive glasses as solid implants in a dental application was examined by Stanley, H., Hench, L. L., Going, R., Bennett, C., Chellemi, S. J., King, C., Ingersoll, N., Etherridge, E., and Kreutziger, K. ["The implantation of natural tooth from bioglasses in baboons," Oral Surg. Oral Med. Oral Path., 42, (3), 339-356, 1976.] Replicate tooth forms of glass were fabricated and implanted into extracted incisor sockets of adult baboons. Distinct histopathologic features were associated with the specific formulation used. After six months, the F glass formulation induced ankylosis while another glass formulation induced a fibrous capsule. In the two successful S implants, ankylosis was induced in one with the other producing an apparently normal periodontal ligament. A two year study [Stanley, H. R., Hench, L. L. Bennett, Jr., C. G. Chellemi, S. J. King, C.J. Going, R. E., Ingersoll, N. L., Ethridge, E. C., Kreutziger, K. L., Loeb, L., Clark, A. E.: "The implantation of Natural Tooth From Bioglass in Baboons-Long Term Results," The International Jour of Oral Implantology, pg. 26-36, Vol. 2:2, 1981]consistently found ankylosis of both the F and S formulations.
It is an object of the present invention to provide bioactive and biocompatible glass compositions specifically suitable for the repair of periodontal osseous defects.